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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
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Targeted Metabolomics Analysis Suggests That Tacrolimus Alters Protection against Oxidative Stress

Marie Joncquel1, Julie Labasque1, Julie Demaret2

  • 1CHU Lille, Centre de Biologie Pathologie Génétique, Service Hormonologie Métabolisme Nutrition Oncologie, F-59000 Lille, France.

Antioxidants (Basel, Switzerland)
|July 29, 2023
PubMed

Insights

Tacrolimus (FK506) treatment alters plasma metabolite levels, including increased pipecolic acid (PA) and sarcosine. These changes suggest a link to Peroxisomal sarcosine oxidase (PIPOX) and indicate PA may be an early biomarker for FK506 nephrotoxicity.

Area of Science:

  • Immunology
  • Metabolomics
  • Pharmacology

Background:

  • Tacrolimus (FK506) is a widely used immunosuppressant with dose-dependent side effects.
  • The precise mechanisms of FK506 toxicity remain incompletely understood.
  • Investigating FK506-mediated toxicity is crucial due to its increasing global use.

Purpose of the Study:

  • To explore the toxicity mechanisms of Tacrolimus (FK506) by identifying associated metabolic pathway alterations.
  • To compare metabolic changes in patients treated with FK506 versus Ciclosporin (CSA).
  • To evaluate pipecolic acid (PA) as a potential biomarker for FK506-induced nephrotoxicity.

Main Methods:

  • Targeted metabolomic analysis using Liquid Chromatography-Mass Spectrometry (LC-MS).
  • Analysis of plasma samples from patients undergoing FK506 treatment and a control group.
  • Comparison of metabolic profiles between FK506 and Ciclosporin (CSA) treated patients.

Main Results:

  • Patients on FK506 showed increased plasma concentrations of pipecolic acid (PA) and sarcosine compared to controls.
  • A decrease in the glycine/sarcosine ratio and a tendency for increased plasma lysine were observed in FK506 patients.
  • Plasma PA levels did not increase in patients treated with CSA, suggesting no direct link between calcineurin inhibition and PA elevation.

Conclusions:

  • Metabolomic alterations in FK506-treated patients suggest a potential role for Peroxisomal sarcosine oxidase (PIPOX) in FK506 toxicity.
  • Pipecolic acid (PA) may serve as a valuable early biomarker for nephrotoxicity monitoring in patients receiving FK506.
  • The findings provide new insights into FK506's metabolic impact and potential toxicity pathways.
Keywords:
immunosuppressivemetabolomicsoxidative stresspipecolic acidtacrolimus

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